Post-polio syndrome is characterized by new weakness, fatigue and pain, probably due to a distal degeneration of enlarged motor units occuring through axonal sprouting, as a result of the recovery process from acute paralytic polio. New weakness is likely due to permanent denervation, whereas fatigue may be due to neuromuscular junction (NMJ) transmission defects. The normal aging process, with decreased growth hormone and insulin-like growth factor (IGF-1) which stimulates synthesis of protein and nucleic acids in muscle cells, regeneration of peripheral nerves and sprouting) are possible contributing factors. There is no specific treatment for PS. Pyridostigmine is an anticholineterase which inhibits the hydrolysis of acetylcholine at the NMJ and prolong its effect. It can also enhance growth hormone secretion in growth hormone deficiency states. Preliminary work indicates that a) NMJ transmission defects can ameliorate with anticholinesterase agents in PPS, b) fatigue in PPS may be due to NMJ transmission defects, and c) approximately 59% of PPS patients respond to pyrodistigmine 180mg/day in an open trial.